A significant problem with many candidate drugs, or even drugs in clinical use, is insufficient or unsatisfactory in vivo efficacy. Insufficient in vivo efficacy can be manifested in a variety of ways, such as (i) low bioavailability of the active compound; (ii) undesirably short half-life of the active compound, (iii) and/or undesirably high systemic toxicity of the active compound. To avoid eliminating otherwise promising drugs from clinical use, there remains a need for new approaches to enhancing the in vivo efficacy of active compounds in their delivery to human and animal subjects.
U.S. Pat. No. 6,004,782 to Danielle et al. describes bioelastic polypeptides and the expression thereof in host cells. The use thereof as fusion proteins containing therapeutics is described in a cursory fashion at column 15, lines 43-53 therein. Enhancing the in vivo efficacy of an active agent is neither suggested nor described.
U.S. Pat. No. 6,582,926 to Chilkoti describes, among other things, methods of targeting compounds to regions of interest in a subject by administering the compound to be delivered as a conjugate with a polymer that undergoes an inverse temperature transition (such as an ELP). Compounds to be delivered include certain radionuclides, chemotherapeutic agents, cytotoxic agents, and imaging agents as set forth at column 11, lines 6-21. Enhancing the in vivo efficacy of an active agent is neither suggested nor described.
U.S. Pat. No. 6,852,834 to Chilkoti describes, among other things, fusion proteins that are isolatable by phase transition, primarily to improve the yield thereof during manufacturing. Fusion proteins of therapeutic proteins are generally described at column 11, lines 10-24. Enhancing the in vivo efficacy of an active agent is neither suggested nor described.